Roles of tau pathology in the locus coeruleus (LC) in age-associated pathophysiology and Alzheimer’s disease pathogenesis: Potential strategies to protect the LC against aging
Roles of tau pathology in the locus coeruleus (LC) in age-associated pathophysiology and Alzheimer’s disease pathogenesis: Potential strategies to protect the LC against aging
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DOI：
10.1016/j.brainres.2017.12.027
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发表时间：
2017-12
期刊：
影响因子：
2.9
通讯作者：
A. Satoh;Koichi M. Iijima
中科院分区：
文献类型：
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作者：
A. Satoh;Koichi M. Iijima
蓝斑（LC）是脑干中含有去甲肾上腺素（去甲肾上腺素，NE）的核团，并受神经支配进入广泛的大脑区域。这种LC-NE系统在各种大脑功能中起着关键作用，包括注意力，唤醒，情感，认知和睡眠-觉醒周期。LC是易发生神经元缠结（NFT）的脑区域之一，其与“原发性年龄相关性tau蛋白病（PART）”相关，所述原发性年龄相关性tau蛋白病描述了在老年个体的脑中通常观察到的病理学。在阿尔茨海默氏病（AD）中，LC是发展NFT的第一个地方之一，其可以充当淀粉样蛋白-β（Aβ）积累后随后在整个脑中传播病理的种子。随着AD的进展，LC中发生显著的神经元损失。此外，LC神经变性不仅是AD的结果，而且还驱动AD的临床和病理表现，例如小胶质细胞失调、睡眠障碍、认知下降和神经血管功能障碍。因此，预防LC-NE系统中的NFT病理和神经元损失对于抑制AD的进展至关重要。我们建议，针对老化本身可能是一种积极的干预措施，对年龄相关的变化，在LC。这种方法可以为针对年龄相关的神经退行性疾病，特别是AD的新干预开辟道路。
The locus coeruleus (LC) is the noradrenaline (norepinephrine, NE)-containing nucleus in the brainstem and innervates into widespread brain regions. This LC-NE system plays a critical role in a variety of brain functions, including attention, arousal, emotion, cognition, and the sleep-wake cycle. The LC is one of the brain regions vulnerable to the occurrence of neurofibrillary tangles (NFTs), which is associated with “primary age-related tauopathy (PART)” that describes the pathology commonly observed in the brains of aged individuals. In Alzheimer’s disease (AD), the LC is one of the first places to develop NFTs, which may act as a seed for subsequent spreading of the pathology throughout the brain upon amyloid-β (Aβ) accumulation. As AD progresses, significant neuron loss occurs in the LC. Moreover, LC neurodegeneration is not only a consequence of AD, but also drives clinical and pathological manifestations of AD, such as microglial dysregulation, sleep disturbance, cognitive decline, and neurovascular dysfunction. Therefore, prevention of NFT pathology and neuron loss in the LC-NE system is critical for suppressing the progression of AD. We propose that targeting aging itself may be a proactive intervention against age-associated changes in the LC. Such an approach could open the way for novel interventions against age-associated neurodegenerative disorders, in particular, AD.